an efficacy and safety study of jnj-56021927 (apalutamide) in high-risk prostate cancer subjects receiving primary radiation therapy: atlas

Conditions: Prostatic Neoplasms

Summary: the purpose of this study is to determine if apalutamide plus gonadotropin releasing hormone (gnrh) agonist in participants with high-risk, localized or locally advanced prostate cancer receiving primary radiation therapy (rt) results in an improvement of metastasis-free survival based on conventional or prostate specific membrane antigen-positron emission tomography (psma-pet) imaging evaluated by blinded independent central review (bicr).

this is a randomized, double-blind, placebo-controlled, multicenter study of apalutamide plus gnrh agonist compared with gnrh agonist among participants with high-risk, localized or locally advanced prostate cancer receiving primary radiation therapy (rt). the study will include a screening phase, treatment phase, a posttreatment phase, and a long-term follow-up phase. participants will either receive either apalutamide (experimental) or bicalutamide 50 milligram (mg) capsule plus placebo as control group. safety will be monitored throughout the study.

Eligibility criteria:
inclusion criteria: * age \>= 18 years * indicated and planned to receive primary radiation therapy for prostate cancer * histologically confirmed adenocarcinoma of an intact prostate, and 1 of the following at diagnosis: 1) gleason score \>=8 and \>=ct2c, 2) gleason score \>=7, psa \>=20 nanogram per milliliters (ng/ml), and \>=ct2c * charlson index (cci) \<=3 * an eastern cooperative oncology group (ecog) performance status (ps) grade of 0 or 1 * adequate organ function: (1) aspartate aminotransferase (ast), alanine aminotransferase (alt), within normal limits (wnl), (2) serum creatinine less than (\ =)140,000/microliter (mcl), independent of transfusion and/or growth factors within 3 months prior to randomization, (4) hemoglobin \>= 12.0 gram/deciliter (g/dl) (7.4 millimloes \[mmol\], independent of transfusion and/or growth factors within 3 months prior to randomization * participants who are sexually active (even men with vasectomies) and willing to use a condom and agree not to donate sperm during the trial * signed, written, informed consent * be able to swallow whole study drug tablets exclusion criteria: - * presence of distant metastasis, (clinical stage m1). isolated pelvic nodal disease below the iliac bifurcation (clinical stage n1) is not an exclusion. diagnosis of distant metastasis (clinical m stage; m0 versus m1a, m1b, m1c) and pelvic nodal disease (clinical n stage; n1 versus n0) will be assessed by central radiological review. patients are considered eligible only if the central radiological review confirms clinical stage m0. * prior treatment with gonadotropin releasing hormone (gnrh) analogue or anti-androgen or both for \>3 months prior to randomization * bilateral orchiectomy * history of pelvic radiation * prior systemic (example \[e.g.\], chemotherapy) or local (e.g. radical prostatectomy, cryotherapy) treatment for prostate cancer * history of seizure or any condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness \<= 1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect) * prior treatment with enzalutamide, abiraterone acetate, orteronel, galeterone, ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and progestational agents (including cyproterone acetate) for prostate cancer * prior treatment with radiopharmaceutical agents (e.g., strontium-89) or immunotherapy (e.g., sipuleucel-t) for prostate cancer * prior treatment with systemic glucocorticoids ≤4 weeks prior to randomization or is expected to require long-term use of corticosteroids during the study * use of 5-alpha reductase inhibitors (e.g., dutasteride, finasteride) \<=4 weeks prior to randomization * use of any investigational agent \<=4 weeks prior to randomization * current chronic use of opioid analgesics for \>=3 weeks for oral or \>7 days for non-oral formulations * major surgery \<=4 weeks prior to randomization * current or prior treatment with anti-epileptic medications for the treatment of seizures * gastrointestinal conditions affecting absorption * known or suspected contraindications or hypersensitivity to apalutamide, bicalutamide or gnrh agonists or any of the components of the formulations * any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject

Keywords: prostatic neoplasms prostate cancer high-risk prostate cancer jnj-56021927 apalutamide atlas radiation long-term hormone therapy localized or locally advanced prostate cancer janssen